肿瘤微环境中的氧化应激及其与癌症免疫治疗的相关性。
Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy.
作者信息
Aboelella Nada S, Brandle Caitlin, Kim Timothy, Ding Zhi-Chun, Zhou Gang
机构信息
Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
The Graduate School, Augusta University, Augusta, GA 30912, USA.
出版信息
Cancers (Basel). 2021 Feb 27;13(5):986. doi: 10.3390/cancers13050986.
It has been well-established that cancer cells are under constant oxidative stress, as reflected by elevated basal level of reactive oxygen species (ROS), due to increased metabolism driven by aberrant cell growth. Cancer cells can adapt to maintain redox homeostasis through a variety of mechanisms. The prevalent perception about ROS is that they are one of the key drivers promoting tumor initiation, progression, metastasis, and drug resistance. Based on this notion, numerous antioxidants that aim to mitigate tumor oxidative stress have been tested for cancer prevention or treatment, although the effectiveness of this strategy has yet to be established. In recent years, it has been increasingly appreciated that ROS have a complex, multifaceted role in the tumor microenvironment (TME), and that tumor redox can be targeted to amplify oxidative stress inside the tumor to cause tumor destruction. Accumulating evidence indicates that cancer immunotherapies can alter tumor redox to intensify tumor oxidative stress, resulting in ROS-dependent tumor rejection. Herein we review the recent progresses regarding the impact of ROS on cancer cells and various immune cells in the TME, and discuss the emerging ROS-modulating strategies that can be used in combination with cancer immunotherapies to achieve enhanced antitumor effects.
众所周知,癌细胞处于持续的氧化应激状态,这表现为活性氧(ROS)的基础水平升高,这是由于异常细胞生长驱动的代谢增加所致。癌细胞可以通过多种机制适应以维持氧化还原稳态。关于ROS的普遍看法是,它们是促进肿瘤起始、进展、转移和耐药性的关键驱动因素之一。基于这一概念,许多旨在减轻肿瘤氧化应激的抗氧化剂已被测试用于癌症预防或治疗,尽管这一策略的有效性尚未确定。近年来,人们越来越认识到ROS在肿瘤微环境(TME)中具有复杂、多方面的作用,并且肿瘤氧化还原可以作为靶点来放大肿瘤内部的氧化应激以导致肿瘤破坏。越来越多的证据表明,癌症免疫疗法可以改变肿瘤氧化还原以加剧肿瘤氧化应激,从而导致依赖ROS的肿瘤排斥反应。在此,我们综述了关于ROS对TME中癌细胞和各种免疫细胞影响的最新进展,并讨论了可与癌症免疫疗法联合使用以实现增强抗肿瘤效果的新兴ROS调节策略。